1. Field of the Invention
This invention relates to a new method for treating autoimmune diseases such as hypertension, diabetes and lupus. Treatment requires the administration of a Thymus gland extract, designated Thymosin.
2. Description of the Prior Art
The importance of the thymus gland in the development and senesince of immunological competence in mammals is now generally accepted. Although the exact mechanism by which the thymus gland exerts control over the immune system is not known, it appears that a substantial portion of this control occurs via a hormonal mechanism. The thymus produces a family of polypeptides termed thymosin and perhaps several other thymic hormones and/or factors which play an important role in the maturation, differentiation and function of T-cells (Thymus-derived cells) and the immune response.
Thymosin, fraction 5, which has been widely employed in the biological investigations of thymosin, has been shown to contain 10-15 major components and 20 or more minor components, with molecular weights ranging from 1,000 to 15,000, as determined by analytical polyacrylamide gel electrophoresis and isoelectric focusing. Thymosin purification, characterization, and use is described in greater detail by Goldstein et al in U.S. Pat. Nos. 4,010,148 and 4,079,127 herein incorporated by reference. These patents describe the purification and use of Thymosin, and one of its components, Thymosin .alpha..
Thymosin, fraction 5, refers to the fifth step in purification, that is, the product following the ultrafiltration and gel filtration (sephadex G-25) desalting of an ammonium sulfate precipitate from a thymus gland extract as shown below.
______________________________________ Steps in Thymosin Purification ______________________________________ Fraction 1 14,000 .times. g Centrifugation Product Fraction 2 80.degree. C. Heat step filtrate Fraction 3 Acetone Precipitate Fraction 4 Ammonium sulfate precipitate Fraction 5 Ultrafiltration & Sephadex G25 desalted peak ______________________________________
Thymosin, fraction 5, and Thymosin .alpha., have been used to reconstitute immune functions in mammals lacking some Thymosin-dependent function which causes an immune disease such as Thymus hypoplasia and abnormal immunoglobulin synthesis. Thymosin, fraction 5, has also been used in combination with cancer chemotherapy and radiotherapy to prolong survival time. (Journal of the American Medical Association, July 17, 1981, Vol. 246, No. 3, page 205). Apparently Thymosin, fraction 5, contains those hormones necessary for the proper development of particular subsets of T-lymphocytes. Thymosin .alpha., has been shown to circulate at high levels in newborn children but to decline with age. The other hormonal elements present in Thymosin, fraction 5, have not been purified or well characterized. Thus the properties of Thymosin, fraction 5, may be due to a combination of one or more of the hormone-like polypeptides present. However, the prior disclosures of the use of thymus extracts such as Thymosin, fraction 5, did not disclose the treatment of autoimmune diseases.
An autoimmune disease involves an animal's immune system harmfully attacking the tissues of its own body. Therefore, a fraction active in stimulating the immune response, such as Thymosin, might be anticipated to aggravate and increase the pathology in an autoimmune disease. Surprisingly, Thymosin, fraction 5 acts to decrease autoimmunity. This unexpected result could only be discovered through the use of a particular animal disease model system such as the spontaneous hypertensive rat (SHR) system. In a normal animal, Thymosin, fraction 5, would not have any observable effect on hypertension because the animal would have normal blood pressure. Thus, the use of a model such as the SHR system was necessary to detect the anti-autoimmune affects of Thymosin, fraction 5. Previously, it was not recognized that hypertension, diabetes and other disease states had an autoimmune component as their cause. Therefore, an unrecognized need for Thymosin treatment existed and recognition of this need and the effectiveness of Thymosin treatment of autoimmune diseases are the central concepts of this invention.